There are many """"""""allergic"""""""" models of asthma available which are widely used in studies seeking to understand mechanisms of airway hyperreactivity. Although antigen challenge in these models mimics some aspects of acute human asthma, these models lack the nonspecific airway hyperreactivity, characteristic of the human disease. While studies in such models contribute to our understanding of the complexity of the immune response, they tell us little about airway hyperreactivity. This severely limits their usefulness as models. In contrast, our Basenji-Greyhound (BG) crossbred dogs demonstrate persistent nonspecific airway hyperreactivity, separate from allergy, making our model an ideal situation to elucidate mechanisms underlying airway hyperreactivity. The discovery of this dog population with persistent airway hyperreactivity is a significant advance in this field. The ability to pass on this trait to the offspring ensures a continuing supply of these animals. This provides us with a unique opportunity to understand the defect underlying airway hyperractivity in these dogs and perhaps in man, thus leading to better methods of preventing and treating a common chronic disabling disease. We have shown that airway hyperreactivity in these dogs is not directly associated with increased parasympathetic nervous system activity, increased lung epithelial permeability in the absence of airway challenge, or an intrinsic defect in the airway smooth muscle. Our studies with citric acid aerosols suggest that mediators are involved and that calcium shifts inside some airway cell are responsible for release. Preliminary data suggest anatomic abnormalities in the arrangement of muscle bundles, elastic fibers and epithelium of the airway of BG dogs. Over the next five years we plan to determine which of the possible mediators are important in airway hyperreactivity in the BG dog model of asthma. We plan to measure from the bronchoalveolar fluid many of these mediators directly and the rest by bioassay after immunological and non-immunological aerosol challenge. We plan to identify the cell in the airway from which these mediators are derived and to relate these events to a structural or functional difference in an airway cell or structure of BG compared to non-BG dogs.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Sauder, R A; Lenox, W C; Tobias, J D et al. (1993) Methylprednisolone increases sensitivity to beta-adrenergic agonists within 48 hours in Basenji greyhounds. Anesthesiology 79:1278-83
Lindeman, K S; Hirshman, C A; Freed, A N (1991) Functional antagonism of airway constriction in the canine lung periphery. J Appl Physiol 71:1848-55
Lindeman, K S; Hirshman, C A; Freed, A N (1991) Calcium channel blockers modulate airway constriction in the canine lung periphery. J Appl Physiol 70:624-30
Lindeman, K S; Hirshman, C A; Freed, A N (1990) Calcium chelators induce bronchoconstriction in the canine lung periphery. J Appl Physiol 68:1114-20
Kaise, A; Weinmann, G G; Levitt, R C et al. (1990) Succinylcholine potentiates responses to intravenous acetylcholine in the canine lung periphery. J Appl Physiol 69:1137-42
Tobias, J D; Sauder, R A; Hirshman, C A (1990) Reduced sensitivity to beta-adrenergic agonists in Basenji-Greyhound dogs. J Appl Physiol 69:1212-9
Sauder, R A; Hirshman, C A (1990) Protamine-induced histamine release in human skin mast cells. Anesthesiology 73:165-7
Tobias, J D; Sauder, R A; Hirshman, C A (1990) Pulmonary reactivity to methacholine during beta-adrenergic blockade: propranolol versus esmolol. Anesthesiology 73:132-6
Tobias, J D; Hirshman, C A (1990) Attenuation of histamine-induced airway constriction by albuterol during halothane anesthesia. Anesthesiology 72:105-10
Tobias, J D; Kubos, K L; Hirshman, C A (1989) Aminophylline does not attenuate histamine-induced airway constriction during halothane anesthesia. Anesthesiology 71:723-9

Showing the most recent 10 out of 14 publications